AB0265 RHEUMATOID ARTHRITIS PATIENTS HOSPITALIZED FOR A SERIOUS INFECTION HAVE HIGH INCIDENCE OF SEPSIS WHILE THOSE ON bDMARDs HAVE LOWER MORTALITY COMPARED TO THOSE ON csDMARDs
Authors: E. Tzagkarakis, I. Flouri, I. Facondi, E. Kalogiannaki, S. Ilia, G. Briassoulis, P. Sidiropoulos
Journal: Annals of the Rheumatic Diseases (2022)

Background The treatment of rheumatoid arthritis (RA) includes conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biologic DMARDs (bDMARDs). RA is associated with an increased risk of serious infections (SI) and the use of bDMARDs almost doubles this risk. SI can lead to sepsis, a life-threatening condition manifested by organ failure caused by a dysregulated host response to a pathogen. bDMARDs target pro-inflammatory cytokines which mediate the inflammation cascade activated both in RA and sepsis. However, very few data exist regarding the incidence of sepsis in patients with a SI while on treatment with bDMARDs. Objectives To assess the outcomes of sepsis and death in RA patients with a SI and compare them between patients on bDMARD and csDMARDs. Secondary aims were the comparison of subgroups of patients treated with different bDMARD classes [Tumor necrosis factor inhibitor (TNFi) vs. non-TNFi] and subgroups based on age (geriatric vs. younger patients). Methods Single-center retrospective analysis of adult RA patients registered in the University of Crete Rheumatology Clinic Registry (UCRCR), who were hospitalized for ≥1 SI between 2004-2020. Patients were assigned to “bDMARD group” if they were receiving bDMARDs at the time of the SI or “Control group” if there was no bDMARD exposure at least 3 months before the SI. Demographics, RA characteristics, and comorbidities were retrieved from UCRCR database, while details regarding hospitalization were sought in the patients’ electronic and paper files. Together with the “Sequential Organ Failure Assessment” (SOFA) criteria at admission and during 76-92 hours of hospitalization used to define the diagnosis of sepsis, we also analyzed the criteria of septic shock and in-hospital mortality. Results A total of 117 hospitalizations for SI in RA patients were included: 66 in patients receiving bDMARDs and 51 in the control group (65% bDMARD-naive and 35% bDMARD-experienced). The majority of the patients (76%) were women in both groups, however, patients on bDMARDs were younger than control patients [70 (IQR 62-77) and 78 (IQR 68-82) years old respectively, p=0.002]. Other demographics, disease characteristics, disease activity at baseline, and comorbidities did not differ between the two groups, except for a higher prevalence of one or more previous hospitalizations for infection in patients on bDMARDs. During hospitalization, 14 patients (12%) died. Mortality was significantly higher in the control group (19.6% of patients) compared to the bDMARD group (6%) (p=0.025). Sepsis criteria were fulfilled in 56 patients (47.9%) at admission and/or at 76-92 hours of hospitalization. Sepsis was marginally more frequent in the control group versus the bDMARD group (56.9% vs. 40.9% respectively, p=0.087). In the subgroup analysis based on the type of bDMARD, no statistical difference was found for the outcomes of sepsis or death between patients on TNFi versus those on non-TNFi. However, in the subgroup of patients ≥65 years old, there was a tendency for a lower incidence of sepsis or death in patients on TNFi compared to those on non-TNFi or the control group [14% vs 53%, vs 85% respectively (p=0.120) for the outcome of sepsis and 7% vs. 21%, vs. 71% (p=0.138) for the outcome of death]. Receiver operating characteristic (ROC) analysis indicated older age (p&lt;0.001), higher SOFA score at admission (p&lt;0.001), septic shock at 76-92 hours (p&lt;0.001), and non-exposure to TNFi (p=0.040) as predictors of in-hospital death. However, in multivariable logistic regression analysis, older age was the only significant predictor of sepsis and death during hospitalization. Conclusion In the present study, we found a high incidence of sepsis (47.9%) and mortality (12%) in RA patients hospitalized for a serious infection. Older age is the most significant predictor of adverse outcomes, however, patients on bDMARDs showed lower mortality and a tendency for a lower incidence of sepsis compared to the control group. Disclosure of Interests None declared